Mutation deep within an intron of MSH2 causes Lynch syndrome

Clendenning, Mark, Buchanan, Daniel D., Walsh, Michael D., Nagler, Belinda, Rosty, Christophe, Thompson, Bryony, Spurdle, Amanda B., Hopper, John L., Jenkins, Mark A. and Young, Joanne P. (2011) Mutation deep within an intron of MSH2 causes Lynch syndrome. Familial Cancer, 10 2: 297-301. doi:10.1007/s10689-011-9427-0

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Author Clendenning, Mark
Buchanan, Daniel D.
Walsh, Michael D.
Nagler, Belinda
Rosty, Christophe
Thompson, Bryony
Spurdle, Amanda B.
Hopper, John L.
Jenkins, Mark A.
Young, Joanne P.
Title Mutation deep within an intron of MSH2 causes Lynch syndrome
Journal name Familial Cancer   Check publisher's open access policy
ISSN 1389-9600
Publication date 2011-06-01
Year available 2011
Sub-type Article (original research)
DOI 10.1007/s10689-011-9427-0
Open Access Status Not yet assessed
Volume 10
Issue 2
Start page 297
End page 301
Total pages 5
Place of publication Dordrecht, GX, Netherlands
Publisher Springer Netherlands
Language eng
Abstract Lynch syndrome, a heritable form of cancer predisposition, is caused by germline mutations within genes of the DNA mismatch repair family, and can be rapidly identified in young onset cancer patients through the detection of loss of expression of at least one of these genes in tumour samples. To date, such causative mutations have only been identified within exonic and splice site regions. Though this approach has been successful in the majority of families, a considerable number remain in which no mutation has been found. To address this situation, we used an alternative mutation discovery procedure which involved haplotype analysis of the locus containing the gene lost in the tumour and delineation of segregating haplotypes, followed by an investigation of splicing aberrations to uncover cryptic splice sites which lay outside the genomic regions routinely examined for mutations. In this report, we show that an intronic mutation 478 bp upstream of exon 2 in the MSH2 gene causes Lynch syndrome through creation of a novel splice donor site with subsequent pseudoexon activation, thus highlighting the need for more extensive sequencing approaches in families where routine procedures fail to find a mutation.
Keyword Oncology
Genetics & Heredity
Genetics & Heredity
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID CA-95-011
U01 CA097735
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
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Created: Wed, 21 Dec 2011, 00:36:19 EST by Matthew Lamb on behalf of School of Medicine